Partial or complete blockage of blood vessels is rapidly becoming a major cause of injury or death. Blood vessel blockages can result in a variety of physical ailments including heart attacks and strokes. Blood vessel blockages may be caused by a variety of agents, including blood clots and the build up of cholesterol on a blood vessel.
Blood vessel blockage is typically treated by bypassing the blocked portion of the blood vessel. The bypass is generally accomplished by using either a graft from a patient's blood vessel or a synthetic conduit.
Alternatively, the blocked portion of the vessel may be reopened or replaced by a vascular stent composed of metal or synthetic materials. In some cases, stents are preferred instead of grafts, because, unlike grafts, stents can be implanted without a surgical procedure. Further, the risks of restenosis (e.g., a narrowing of a blood passageway) is decreased with stents relative to grafts.
The use of stents to reopen or replace the blocked portion of the blood vessel can create complications. Stents can themselves induce partial or complete blocking of the blood vessel by triggering blood clotting in the vicinity of the stent. After implantation, the natural process of fibrin deposition on the stent occurs to initiate the healing process. The deposition of the fibrin in the presence of thrombin triggers platelet activation and the formation of a thrombus or embolus. Bound thrombin can also induce the formation of more fibrin on the stent, thereby narrowing the luminal area of the stent. The reduced luminal area can cause an embolism in the patient.
Several approaches have been employed to overcome the complications associated with vascular stents. In one approach, an anticoagulant is administered to the patient to reduce the likelihood of clotting. Anticoagulants are not widely used because they can cause serious injury or death. In another approach, endothelial cells, the cells lining blood and lymphatic vessels, are seeded onto the stent to facilitate the healing process. The seeding of stents with endothelial cells is also not widely used because seeded stents are difficult, if not impossible, to manufacture. In yet another approach, a fibrin coating is deposited on the stent before implantation to facilitate the healing process. Compared to stents implanted without a fibrin coating, the incorporation of a fibrin coating on an implanted stent reduces significantly the likelihood of blood vessel blockage after implantation.
The approach of forming a fibrin coating on a stent before implantation to reduce or overcome complications has several drawbacks which significantly increase the cost of the fibrin-coated stent. For example, a fibrin coating is unstable outside of the body and generally must be implanted immediately after formation of the coating. A fibrin coating generally does not adhere tightly to the stent and can become dislodged easily from the stent surface. A denatured fibrin coating has been used to enhance adhesion of the coating to the stent surface, but denatured fibrin has a different structure than natured fibrin (e.g., fibrin formed in the body) leading to an increased risk of blood clots. Consequently, denatured fibrin is not as effective as a natured fibrin coating in enhancing healing and reducing the likelihood of blood clotting after implantation.
Accordingly, there is a need for a device to be implanted in a body, such as a stent, having a low risk of inducing blood clot formation after implantation of the device in a body.
There is a further need for an improved method for seeding a device to be implanted in a body with endothelial cells.
There is a further need for a device to be implanted in a body having a fibrin coating that is stable outside the body. There is a related need for a device to be implanted in a body having a fibrin coating that may be stored for long periods before use.
There is a further need for a fibrin coating that has a high degree of adhesion to the surface of the device. There is a related need for a fibrin coating containing a substantial amount of natured fibrin and a limited amount of denatured fibrin.